Fully automated diagnostic analyzers are commercially available to perform chemical assays and immunoassays of biological liquids such as urine, blood serum, plasma, cerebrospinal liquids and the like. Generally, reactions between an analyte in a patient sample and reagents used during the assay generate a signal from which the concentration of analyte in the patient sample may be calculated. Such automated analyzers generally use an aspirating means such as a sampling tip, or probe or needle, to transfer desired volumes of liquid samples or liquid reagents between receptacles, such as between sample containers, reagent containers and reaction cuvettes disposed on the analyzer. Hereinafter, variations of the term aspirate refer to all of such processes for extracting liquid from one container and depositing at least some of the liquid into the same or another container and further includes the supporting devices required to complete the liquid handling operations.
Aspirators typically comprise an elongated, needle-like probe or pipette having a hollow passage whereby liquid may be aspirated into and/or dispensed from the probe using appropriate pumping resources. The pipette may be carried by a transport mechanism adapted to provide horizontal and vertical movement so as to enable the pipette tip to be lowered into a liquid in a reservoir for aspiration of the liquid, and for transporting the liquid to a another location whereat the pipette is lowered to an optimal position for dispensing the liquid. Some type of device, such as a piston assembly, which may be incorporated into the pipette, is operated electronically to aspirate liquid into the pipette and to dispense liquid from the pipette using vacuum pressures.
It is desirable, when aspirating a liquid, to accurately determine if any abnormalities or non-uniformities within the liquid have adversely affected the overall quality of the aspiration process. Non-uniformities such as clogs, clogs, bubbles, abnormal liquid viscosity, insufficient volume, etc, may exist in liquids, particularly when the liquid is one of several body liquids being analyzed as these frequently are of a non-uniform composition. As used herein, the term “clot” is associated with a physical aggregate in an aspirated liquid while a “clog” is associated with any physical impediment to a successful liquid aspiration other than insufficient sample. Various methods have been developed to detect the effect of such non-uniformities on the aspiration process.
U.S. Pat. No. 6,370,942, assigned to the assignee of the present application and incorporated herein by reference, discloses an method for evaluating the quality of a liquid aspiration for undesirable events such as partial or complete clogs, or aspiration of air by employing three separate aspiration tests including a pressure difference test to verify liquid was aspirated, a pressure recovery test to check for clogs and aspiration of unwanted cells, and a pressure shape test to check for abnormalities during aspiration, such as clogs, air aspiration, density changes (due to aspiration of blood cells), etc.
U.S. Pat. No. 6,022,747 discloses a blood clog detector having a pressure transducer on an aspiration line to provide output voltage data to a microprocessor corresponding to the vacuum level during aspiration. The microprocessor integrates the vacuum readings over time during the aspiration cycle to provide a pressure integral for each test sample aspiration. Acceptability of the test sample for analysis is based upon a predetermined difference between the reference pressure integral and each test sample pressure integral.
U.S. Pat. No. 5,540,081 relates to a pipetting apparatus provided with a pressure sensor and a plurality of pressure difference calculating circuits obtain a pressure difference at a different pressure calculation period. An alarm circuit is included for outputting a clog detection alarm signal when at least one of said discriminating circuits discriminates that the obtained pressure difference exceeds the discrimination threshold value.
U.S. Pat. No. 5,503,036 relates to an obstruction detection circuit for detecting an obstruction of a sample probe of an automated liquid sample aspiration/dispensation device. Pressure within a connecting conduit is measured shortly after the start of the aspiration or dispensation of a sample and again measured after the completion of the aspiration or the dispensation by the pump. If the pressure has not returned to a predetermined range within a predetermined amount of time, an error condition is reported.
U.S. Pat. No. 5,463,895 discloses provides an apparatus and method of detecting non-homogeneity in a liquid sample, such as the presence of foam or bubbles on the surface of the sample, and/or the presence of clogs on the surface or in the bulk of the sample. This method involves determining the ambient air pressure within a pipettor, aspirating air into the pipettor as the pipettor moves towards a sample in container and monitoring for a pressure change in the pipettor to indicate the surface level of the liquid in said container. Pressure changes are monitored after aspiration and compared to predetermined normal aspiration pressure windows.
U.S. published patent application 20070143063, assigned to the assignee of the present application and incorporated herein by reference, discloses a method for verifying the integrity of an aspiration process by determining the profile of an entire aspiration pressure curve and then determining by numerical analysis whether the difference between the actual and the mathematical approximation to a portion of the profile is less than the standard deviation of the residuals of a linear regression analysis of an aspiration pressure curve measured on a sample known to have clogs therein or known to be less than a desired aspiration volume.
As the state of the art in clinical analysis advances, aspirated sample volumes are increasingly smaller, causing pressure differential values for liquids with different viscosities to become more erratic or “noisy”. In addition, pressure profiles of higher viscosity liquids do not reach stable end-point values. Hence, there is a need for a method for differentiating between a clogged liquid sample and a sample having an abnormally elevated viscosity during a liquid aspiration process.